Interactions between AT1R and GRKs: the determinants for activation of signaling pathways involved in blood pressure regulation.

The success of Angiotensin II receptor blockers, specifically Angiotensin II type 1 receptor (AT1R) antagonists as antihypertensive drug emphasizes the involvement of AT1R in Essential hypertension. The structural insights and mutational studies of Ang II-AT1R have brought about the vision to design Ang II analogs that selectively activate the pathways with beneficial and cardioprotective effects such as cell survival and hinder the deleterious effects such as hypertrophy and cell death. AT1R belongs to G-protein coupled receptors and is regulated by G-protein coupled receptor kinases (GRKs) that either uncouples Gq protein for receptor desensitization or phosphorylate C-terminus to recruit β-arrestin for internalization of the receptor.

Functional relevance of promoter CpG island of human Angiotensin II type 1 receptor (AT1R) gene.

Angiotensin II type 1 receptor can activate number of signalling pathways upon stimulation and consequently its involvement in cancer progression have also been revealed. But which epigenetic mechanisms are involved in its regulation, need to be further explored. In-silico analysis revealed a promoter CpG island (CGI) which was cloned and assayed for functional activity using reporter gene system.

Unravelling the Lesser Known Facets of Angiotensin II Type 1 Receptor.

Purpose Of Review: Hypertension is an important risk factor in various pathologies. Despite enormous advancements in health sciences, the number of hypertensive individuals is increasing worldwide. The complex interplay between genetic and epigenetic factors seems to be a promising pathway to exploring the pathophysiology of hypertension.

Parkin mutations in familial and sporadic Parkinson's disease among Indians.

We observed a mutation frequency of 8.5% in Parkin gene among Indian PD patients based on sequencing and gene dosage analysis of its exons. We identified nine point mutations of which seven are novel and hitherto unreported.

Association of N-acetyl transferase 2 gene polymorphism and slow acetylator phenotype with young onset and late onset Parkinson's disease among Indians.

Objectives: To investigate the association of (i) seven SNPs and SNP haplotypes in the phase II conjugating enzyme N-acetyl transferase 2 gene; and (ii) slow acetylator phenotype, with the development of young onset (YO) and late onset (LO) Parkinson's disease (PD) among Indians.

Methods: A total of 267 cases (132 YOPD, age at onset < or =40 years; 135 LOPD, age at onset >40 years) and 324 age and sex matched controls (132 for YOPD and 192 for LOPD) were genotyped for NAT2 SNPs. Allelic, genotypic and haplotypic association was tested by chi2 using a case-control approach.

Complex phenotypes in an Indian family with homozygous SCA2 mutations.

We describe a consanguineous Indian family having spinocerebellar ataxia type 2 (SCA2) expansions with complex phenotypes (early-onset, dopa-responsive parkinsonism, ataxia and retinitis pigmentosa). The two probands having homozygous SCA2 mutations presenting with early-onset dopa-responsive parkinsonism without ataxia develop dyskinesias within a year of starting levodopa. Their siblings, heterozygous for SCA2 mutations, had retinitis pigmentosa with or without ataxia.